Stromal lymphocyte infiltration after neoadjuvant chemotherapy is associated with aggressive residual disease and lower disease-free survival in HER2-positive breast cancer
Menée à partir de microbiopsies tumorales et d'échantillons de résection provenant de 175 patientes atteintes d'un cancer primitif du sein HER2- et ayant reçu une chimiothérapie néo-adjuvante en combinaison ou non avec le trastuzumab, cette étude française met en évidence une association entre l'infiltration du stroma de la tumeur par les lymphocytes après le traitement néo-adjuvant et la présence d'une maladie résiduelle agressive ou une réduction de la survie sans maladie
Background : The role of tumor-infiltrating lymphocytes (TILs) in breast cancer has been extensively studied over the last decade. High TILs levels have been associated with pathological response rate in the neoadjuvant setting and with better outcomes in the adjuvant setting. However, little attention has been paid to changes in TILs and residual TIL levels after neoadjuvant chemotherapy (NAC). We investigated TIL levels before, after chemotherapy, and their dynamics during treatment, and we assessed the correlation of these levels with response to NAC and prognosis.
Materials and methods : We identified 175 patients with primary HER2- positive breast cancers receiving NAC +/- trastuzumab between 2002 and 2011. Microbiopsy specimens and paired surgical samples were evaluated for stromal lymphocyte infiltration. Univariate and multivariate analyses were performed to assess the association of clinical and pathological factors with pathological complete response (pCR) and disease free survival (DFS).
Results : Baseline TIL levels were not significantly associated with pCR. TIL levels decreased during treatment in 78% of the patients. The magnitude of the decrease was strongly associated with pCR. After chemotherapy, TIL levels were high in tumors displaying agressive patterns (high residual cancer burden score, mitotic index >22, tumor cellularity >5%). In the population with residual disease, TIL levels >25% at the end of NAC were significantly associated with an adverse outcome (TILs>25%, HR = 7.98, p = 0.009) after multivariate analyses including BMI, post-NAC mitotic index and tumor grade.
Conclusion : A decrease in TIL levels during chemotherapy was positively associated with response to treatment. In tumor failing to achieve pCR, post-NAC lymphocytic infiltration was associated with higher residual tumor burden and adverse clinical outcome. Further studies are required to characterize immune infiltration in residual disease to identify candidates who could benefit from second-line therapy trials including immune checkpoint inhibitors.
Annals of Oncology , résumé, 2016